The objective of this research is to continue development of an integrated approach to blood pump development, in order to reduce the incidence of thromboembolic and flow-related adverse events in patients. We have previously applied a similar approach to reducing thromboembolism in a pulsatile left ventricular assist device (LVAD). In this project we will apply these methods to an innovative rotary shear flow LVAD. The specific aims are to: 1) Extend a computational fluid dynamics (CFD) model developed for pulsatile pumps to a unique rotary blood pumps. Validation and refinement will be based on experimental fluid dynamic (EFD) measurements of hemodynamic performance, fluid velocities, wall shear and Reynolds stresses, using particle image velocimetry (PIV) and laser Doppler velocimetry (LDV), and in-vitro hemolysis testing. 2) Incorporate a TSP thrombosis model, platelet activation model and hemolysis model into our computational fluid dynamics (CFD) code by extending models we have used for pulsatile pump flows, to the flow regimes of rotary blood pumps. We will utilize in vitro tests (rotary disc) of shear-dependent platelet adhesion, and in vitro hemolysis studies to calibrate/validate the model. 3) Perform in vivo studies of complete VAD systems in non-anticoagulated animals to 1) assess location, severity, and time course of thrombosis and embolization, 2) study the effect of pump speed and pulsatile flow, and 3) measure platelet activation, global coagulation, hemolysis, and biomarkers of renal ischemia. 4) Utilize the CFD and computational modeling methods, developed and validated with data from the in vitro and in vivo test methods, to optimize the shear flow cone disc design to minimize thrombosis. A Design of Experiment (DOE) factorial design technique will be used to develop a test plan based upon a weighted cost function. This research will yield improved methods for design, analysis, and testing that will be applicable to a broad range of rotary and pulsatile devices.